Lineage-dependent differences in the disease progression of Zika virus infection in type-I interferon receptor knockout (A129) mice

Stuart Dowall*, Victoria A. Graham, Emma Rayner, Laura Hunter, Barry Atkinson, Geoff Pearson, Michael Dennis, Roger Hewson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)


Zika virus (ZIKV) falls into two lineages: African (ZIKVAF) and Asian (ZIKVAS). These lineages have not been tested comprehensively in parallel for disease progression using an animal model system. Here, using the established type-I interferon receptor knockout (A129) mouse model, it is first demonstrated that ZIKVAFcauses lethal infection, with different kinetics of disease manifestations according to the challenge dose. Animals challenged with a low dose of 10 plaque-forming units (pfu) developed more neurological symptoms than those challenged with 5-log higher doses. By contrast, animals challenged with ZIKVASdisplayed no clinical signs or mortality, even at doses of 106pfu. However, viral RNA was detected in the tissues of animals infected with ZIKV strains from both lineages and similar histological changes were observed. The present study highlights strain specific virulence differences between the African and Asian lineages in a ZIKV mouse model.

Original languageEnglish
Article numbere0005704
JournalPLoS Neglected Tropical Diseases
Issue number7
Publication statusPublished - 3 Jul 2017

Bibliographical note

Funding Information:
This work was funded by Grant-In-Aid funding from Public Health England. The funders has no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors would like to thank Steven Pullan, Kuiama Lewandowski and Rory Miles from the PHE genomics group for the sequencing of all of the ZIKV strains used in our studies. The views expressed in this manuscript are those of the authors and do not necessarily reflect those of the employing institute.

Publisher Copyright:
© 2017 Dowall et al.

Copyright 2018 Elsevier B.V., All rights reserved.


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